Brief Title
PXD101 as Second-Line Therapy in Treating Patients With Malignant Mesothelioma of the Chest That Cannot Be Removed By Surgery
Official Title
Phase II Study of PXD101 (NSC 726630) as Second-Line Therapy for Treatment of Patients With Malignant Pleural Mesothelioma
Brief Summary
This phase II trial is studying how well PXD101 works as second-line therapy in treating
patients with malignant mesothelioma of the chest that cannot be removed by surgery. PXD101
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and
by blocking blood flow to the tumor.
Detailed Description
PRIMARY OBJECTIVES:
I. Determine the objective response rate in patients with unresectable malignant pleural
mesothelioma (MPM) treated with PXD101.
SECONDARY OBJECTIVES:
I. Determine the overall survival and time to progression in these patients. II. Assess the
toxicities associated with this drug in these patients. III. Perform molecular correlative
studies on tumor tissue (optional) and peripheral blood (required) and identify potential
predictive markers for response.
OUTLINE:
Patients receive PXD101 IV over 30 minutes on days 1-5. Treatment repeats every 21 days for
up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection during course 1 of treatment for biomarker correlative
studies. Fetal hemoglobin (hemoglobin F) levels are measured via reverse
transcriptase-polymerase chain reaction as a potential predictive marker for response.
After completion of study treatment, patients are followed periodically.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Objective Tumor Response Rate According to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Secondary Outcome
Overall Survival
Condition
Advanced Malignant Mesothelioma
Intervention
belinostat
Study Arms / Comparison Groups
Treatment (belinostat)
Description: Patients receive PXD101 IV at 1000 mg/m2 over 30 minutes on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
13
Start Date
June 2006
Completion Date
March 2009
Primary Completion Date
March 2009
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically confirmed malignant pleural mesothelioma (MPM) of any
of the following subtypes:
- Epithelial
- Sarcomatoid
- Mixed
- Have received only 1 prior systemic chemotherapy regimen for advanced mesothelioma
- Prior intrapleural cytotoxic agents (including bleomycin) not considered systemic
chemotherapy
- Patients who are not candidates for combination chemotherapy are eligible even if
they have not received prior chemotherapy
- Unresectable disease
- Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by
conventional techniques OR >= 10 mm by spiral CT scan
- The sole site of measurable disease must not be located within the radiotherapy
port
- No known brain metastases
- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
- Life expectancy > 3 months
- WBC >= 3,000/mm^3
- Absolute neutrophil count >= 1,500/mm^3
- Platelet count >= 100,000/mm^3
- Bilirubin normal
- AST/ALT =< 2.5 times upper limit of normal
- Creatinine normal OR creatinine clearance >= 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-barrier contraception for 1 week before,
during, and for >= 2 weeks after completion of study treatment
- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to PXD101
- No symptomatic congestive heart failure
- No congestive heart failure related to primary cardiac disease
- No unstable angina pectoris
- No cardiac arrhythmia
- No condition requiring anti-arrhythmic therapy
- No uncontrolled hypertension
- No myocardial infarction within the past 6 months
- No ischemic or severe valvular heart disease
- No ongoing or active infection
- No marked baseline prolongation of QT/QTc interval
- No repeated QTc interval > 500 msec
- No long QT syndrome
- No other significant cardiovascular disease
- No other uncontrolled intercurrent illness
- No psychiatric illness or social situation that would preclude study compliance
- Recovered from prior therapy
- No prior valproic acid or other known histone deacetylase (HDAC) inhibitor
- More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
- More than 3 weeks since prior radiation therapy
- No concurrent medication that may cause torsade de pointes
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Suresh Ramalingam, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00365053
Organization ID
NCI-2012-02839
Secondary IDs
PHII 67
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Suresh Ramalingam, Principal Investigator, City of Hope Medical Center
Verification Date
May 2018